FLUOROURACIL

Posology Adults This medicine is for topical application. Pre-malignant conditions The cream should be applied thinly to the affected area once or twice daily; an occlusive dressing is not essential. Malignant conditions The cream should be applied once or twice daily under an occlusive dressing where this is practicable.

The cream should not harm healthy skin. Treatment should be continued until there is marked inflammatory response from the treated area, preferably with some erosion in the case of pre-malignant conditions. Severe discomfort may be alleviated by the use of topical steroid cream.

The usual duration of treatment for an initial course of therapy is three to four weeks, but this may be prolonged. Lesions on the face usually respond more quickly than those on the trunk or lower limbs whilst lesions on the hands and forearms respond more slowly.

Healing may not be complete until one or two months after therapy is stopped. Special population Elderly Many of the conditions for which fluorouracil is indicated are common in the elderly. No special precautions are necessary. Paediatric population In view of the lack of clinical data available, fluorouracil is not recommended for use in children.

Method of application The hands should be washed carefully after applying this medicine. Also care should be taken to avoid contact with mucous membranes or the eyes when applying the cream. The total area of skin being treated with this medicine at any one time should not exceed 500 cm2 (approximately 23 x 23 cm).

Larger areas should be treated a section at a time.

4) which are related to pharmacological activity of fluorouracil on the skin are the most frequently reported reactions. Allergic type skin reactions and reactions related to systemic drug toxicity are very rarely reported. , pancytopenia, neutropenia, thrombocytopenia, leukocytosis.

, Hypersensitivity and Type IV hypersensitivity).

Nervous system disorders Frequency not known:

Dysgeusia, headache, dizziness.

Eye disorders Frequency not known:

Conjunctival irritation, keratitis, increased lacrimation.

Gastrointestinal disorders Very rare:

Diarrhoea haemorrhagic, diarrhoea, vomiting, abdominal pain, stomatitis, associated with systemic drug toxicity.

Frequency not known:

Nausea.

Skin and subcutaneous tissue disorders Very rare:

Pruritus, urticaria, rash (usually local but also generalised if associated with systemic drug toxicity); erythemas including erythema multiforme; dermal and epidermal conditions (such as skin burning sensation, skin exfoliation, skin swelling); skin and subcutaneous skin ulcerations; dermatitis and eczema conditions (such as contact dermatitis, skin irritation); blisters, and alopecia.

Exposure to sunlight may increase the intensity of the reaction. 4 General disorders and administration site conditions Very rare: Pyrexia, chills and mucosal inflammation, associated with systemic drug toxicity.

Frequency not known:

Application site haemorrhage Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

The normal pattern of response includes: early and severe inflammatory phases (typically characterised by erythema, which may become intense and blotchy), a necrotic phase (characterised by skin erosion) and finally healing (when epithelialisation occurs).

The clinical manifestation of response usually occurs in the second week of fluorouracil treatment. 8). Occlusive dressing may increase inflammatory reactions of the skin. 2). Further application of fluorouracil cream should be avoided in cases of severe skin inflammation including ulceration and blistering.

Instruct patients not to smoke or go near naked flames - risk of severe burns. Fabric (clothing, bedding, dressings etc) that has been in contact with this product burns more easily and is a serious fire hazard. Washing clothing and bedding may reduce product build-up but not totally remove it.

g. natural sunlight, tanning salon) should be avoided. Pre-existing subclinical lesions may become apparent following fluorouracil use. Any severe skin discomfort during treatment with fluorouracil may be alleviated by the use of an appropriate topical steroid cream.

When used according to the approved prescribing information this medicine should have minimal effect on healthy skin. Significant systemic drug toxicity is unlikely via percutaneous absorption of fluorouracil when this medicine is administered as per the approved prescribing information.

g. cuts), if the product is applied under an occlusive dressing, and/or in individuals with deficiency in dihydropyrimidine dehydrogenase (DPD). DPD is a key enzyme involved in metabolising and eliminating fluorouracil. Determination of DPD activity may be considered where systemic drug toxicity is confirmed or suspected.

There have been reports of increased toxicity in patients who have reduced activity of the enzyme dihydropyrimidine dehydrogenase. In the event of suspected systemic drug toxicity, fluorouracil treatment should be stopped. An interval of at least four weeks should elapse between treatment with brivudine, sorivudine or analogues and subsequent administration of fluorouracil.

1. g. brivudine and analogues) may lead to a substantial increase in plasma levels of fluorouracil and associated toxicity and is contraindicated. 5) Use of fluorouracil during pregnancy and in breast-feeding mothers is contraindicated.